Secreted frizzled-related protein 5 (SFRP5)

Secreted frizzled-related protein 5 (**SFRP5**) is a soluble glycoprotein encoded by the SFRP5 gene in humans[1]. It is part of the SFRP family (SFRP1–SFRP5), characterized by a cysteine-rich domain homologous to Wnt-binding sites on Frizzled receptors and a netrin-like domain in the C-terminus[1][2][3]. SFRP5 is primarily expressed in retinal pigment epithelium and adipocytes, with emerging roles in the pancreas and cardiovascular tissues. By binding Wnt ligands, SFRP5 antagonizes both canonical and non-canonical Wnt signaling, regulating cell fate, cell polarity, organ development, adipocyte differentiation, and tissue inflammation[2][3]. Dysregulation of SFRP5—through altered expression or hypermethylation—is linked to obesity, insulin resistance, type 2 diabetes, cardiovascular risk, fibrosis in multiple organs, and cancer[2][3]. It is being studied as a therapeutic target and biomarker for metabolic and cardiovascular diseases, though translating findings into the clinic remains challenging due to diverse biological effects and limited drug development data[2][3].

Other names

FRP1BSARP3sFRP-5FRP-1bSARP-3Frizzled-related protein 1bSecreted apoptosis-related protein 3

Direct binding to Wnt proteins, preventing Wnt-Frizzled receptor interaction and downstream signaling activation[1][2][3]. Formation of non-functional complexes with Wnt or Frizzled proteins to block signal transduction[2][3]. Repression of JNK pathway by interaction with Wnt5a, leading to anti-inflammatory effects[2].